TY - JOUR
T1 - LncRNA KTN1-AS1 promotes tumor growth of hepatocellular carcinoma by targeting miR-23c/ERBB2IP axis
AU - Zhang, Lei
AU - Wang, Liang
AU - Wang, Yufeng
AU - Chen, Tianxiang
AU - Liu, Runkun
AU - Yang, Wei
AU - Liu, Qingguang
AU - Tu, Kangsheng
N1 - Publisher Copyright:
© 2018 Elsevier Masson SAS
PY - 2019/1
Y1 - 2019/1
N2 - Long non-coding RNAs (lncRNAs) are critical regulators in the tumorigenesis and metastasis of hepatocellular carcinoma (HCC). LncRNA KTN1 antisense RNA 1 (KTN1-AS1) has been reported to play an important role in colorectal cancer and correlates with unfavorable clinical outcomes of head and neck squamous cell carcinoma. However, the clinical significance and functional role of KTN1-AS1 in HCC are still unclear. Here, we found that KTN1-AS1 was a highly expressed lncRNA in HCC according to public available databases and our HCC cohort. Further analyses revealed that higher expression of KTN1-AS1 was observed in HCC tissues with large tumor size, high tumor grade and advanced TNM stage. Analysis of survival data indicated that high KTN1-AS1 expression was prominently correlated with poor clinical outcomes of HCC patients. Functionally, KTN1-AS1 knockdown suppressed cell proliferation and colony formation, and increased apoptosis of SMMC-7721 cells in vitro. Furthermore, silencing of KTN1-AS1 restrained tumor growth of HCC in vivo. Conversely, forced expression of KTN1-AS1 facilitated Huh7 cell proliferation and inhibited apoptosis. Mechanistically, KTN1-AS1 inversely regulated miR-23c abundance in HCC cells. Further evidence supported that KTN1-AS1 acted as a competing endogenous RNA (ceRNA) by directly sponging miR-23c in HCC cells. Interestingly, erbb2 interacting protein (ERBB2IP), a known target of miR-23c, was positively regulated by KTN1-AS1 and its restoration reversed KTN1-AS1 knockdown attenuated HCC cell growth. To conclude, our study sheds light on the novel function and underlying mechanism of KTN1-AS1 in HCC, which may accelerate the development of cancer therapy.
AB - Long non-coding RNAs (lncRNAs) are critical regulators in the tumorigenesis and metastasis of hepatocellular carcinoma (HCC). LncRNA KTN1 antisense RNA 1 (KTN1-AS1) has been reported to play an important role in colorectal cancer and correlates with unfavorable clinical outcomes of head and neck squamous cell carcinoma. However, the clinical significance and functional role of KTN1-AS1 in HCC are still unclear. Here, we found that KTN1-AS1 was a highly expressed lncRNA in HCC according to public available databases and our HCC cohort. Further analyses revealed that higher expression of KTN1-AS1 was observed in HCC tissues with large tumor size, high tumor grade and advanced TNM stage. Analysis of survival data indicated that high KTN1-AS1 expression was prominently correlated with poor clinical outcomes of HCC patients. Functionally, KTN1-AS1 knockdown suppressed cell proliferation and colony formation, and increased apoptosis of SMMC-7721 cells in vitro. Furthermore, silencing of KTN1-AS1 restrained tumor growth of HCC in vivo. Conversely, forced expression of KTN1-AS1 facilitated Huh7 cell proliferation and inhibited apoptosis. Mechanistically, KTN1-AS1 inversely regulated miR-23c abundance in HCC cells. Further evidence supported that KTN1-AS1 acted as a competing endogenous RNA (ceRNA) by directly sponging miR-23c in HCC cells. Interestingly, erbb2 interacting protein (ERBB2IP), a known target of miR-23c, was positively regulated by KTN1-AS1 and its restoration reversed KTN1-AS1 knockdown attenuated HCC cell growth. To conclude, our study sheds light on the novel function and underlying mechanism of KTN1-AS1 in HCC, which may accelerate the development of cancer therapy.
KW - ERBB2IP
KW - Hepatocellular carcinoma
KW - KTN1-AS1
KW - Tumor growth
KW - miR-23c
UR - https://www.scopus.com/pages/publications/85056179945
U2 - 10.1016/j.biopha.2018.10.105
DO - 10.1016/j.biopha.2018.10.105
M3 - 文章
C2 - 30551364
AN - SCOPUS:85056179945
SN - 0753-3322
VL - 109
SP - 1140
EP - 1147
JO - Biomedicine and Pharmacotherapy
JF - Biomedicine and Pharmacotherapy
ER -
